The primary mission of the Animal Models Core (Core C) is to conduct animal challenge trials in support of studies by investigators within the RMRCE, at other RCEs and with other governmental, private and academic institutions. These services will be tailored to the needs of the investigator and program, ranging from simple morbidity and mortality experiments, to more complex studies involving aerosol challenges, intense clinical evaluation (i.e. blood sampling over time, telemetric monitoring, hematology), necropsy, histopathologic evaluation and organ pathogen loads. The work will be fee-for-service to investigators, with different fee schedules for RCE and US government investigators versus those from non-RCE academic institutions and commercial entities. In addition to this primary focus on service, Core C personnel will: 1) Assist investigators in the design of appropriate animal experiments, including writing the animal use, select agent and animal budget portions of proposals. This is viewed as a valuable and important service which will ultimately augment program income and contribute to the biodefense effort. 2) Establish new, and enhance existing, rodent models in response to or anticipation of investigator needs. One goal for Year 1 will be to establish, for selected bacterial pathogens, the maximum interval postchallenge at which initiation of high-dose (relevant) antibiotic therapy will allow survival; these data will provide reference points to assist in designing and conducting trials to evaluate therapeutic agents to be applied post-exposure. Another example of enhancing current models will be to characterize the hematologic and clinical chemistry alterations associated with disease pathogenesis; again, this will be valuable in evaluating efficacy of pharmacologic or immunologic interventions. 3) Promote the use of non-rodent models for certain pathogens. Such models could provide large quantities of serum and other samples as reference reagents and to test diagnostic platforms, to provide natural host bases for vaccine and therapeutic trials, and to allow realistic ICU-type monitoring in trials designed to evaluate therapies for human use. Core C is uniquely positioned among RCEs to provide such capabilities. Core C will support all three of the RMRCE Integrated Research Foci on Immunomodulation, Adjuvants and Vaccines (IRF 1), Bacterial Therapeutics (IRF 2), and Viral Therapeutics (IRF 3). Its resources will be utilized by RPs 1.5, 1.6, 1.7, 1.8, 2.3, 2.6, 2.7, 3.3, 3.5 and 3.6.